The invention relates to chiral diazaphospholidines, to methods for their preparation, and to their use in catalysts for the asymmetric catalysis of organic reactions.
Catalysts for asymmetric transformations are of great value in organic synthesis. The modification of an organometallic system with a suitable enantiomerically pure ligand is perhaps the most effective and efficient means to achieve this. The most popular of the systems reported to date contain ligands based on phosphorus donors, such as phosphines. The combination of ruthenium with the ligand BINAP was reported by Akutagawa S. (Chirality in Industry, Edt. A. N. Collins el al. (1992), J. Wiley and Sons, Chapter 17, pages 325-329).
DuPHOS, 1,2-(phospholano)benzenes have been demonstrated by Burk el al. (J. Am. Chem. Soc. (1993), vol. 115, pages 10125-10138 and (1998), Vol. 120, pages 657-663) and are the subject of U.S. Pat. No. 5,008,457 and U.S. Pat. No. 5,559,267. Such compounds have been found to be commercially useful, especially as hydrogenation catalysts when used in combination with ruthenium or rhodium.
Brunel J. M. et al (Tet. Lett., (1997), Vol. 38, pages 5971-5974) discloses the use of pyridine-phosphine ligands for enantioselective palladium catalysed substitution allylic substitution. The same group have also disclosed the use of diazaoxaphospholidones, Constantieux T. et al (Synlett, (1998), pages 49-50).
Brunel J. M. et al. (Tet. Lett., (1998), Vol. 39, pages 2961-2964) discloses the use of a pentavalent phosphorus system in the form of o-hydroxyphenyl diazaphospholidine oxide. One of the intermediates used to produce such a compound is a hydroxyphenyl diazaphospholidine. However, this later compound was not tested as a catalyst.
Other diazaphospholidines have been disclosed in the article by Tye et al. (Chem. Commun., (1997) pages 1053-1054).
It is an aim of the current invention to provide novel compounds having improved catalytic properties.
It is also an aim of the current invention to identify compounds which are capable of being produced by industrially applicable processes.
Accordingly, a first aspect of the invention provides a chemical compound represented by Formula 1 or Formula 2. 
Where:
A and B are independently selected from C(R22R23) and C(R22R23)C(R24R25) especially CH2 or (CH2)2, preferably A and B are the same; R1, R2, R3, R4, R18, R,9, R20, R21, R22, R23, R24 and R25 each may or may not be present and each may be independently selected from H, halide xe2x80x94OH, xe2x80x94SO2R26 (where R26 is selected from a group as defined for R22, R23, R24 and R25), xe2x80x94SH, xe2x80x94NO2, xe2x80x94NH2, xe2x95x90O, xe2x95x90S, straight chain, branched chain, cyclic, saturated, non-saturated, substituted or non-substituted alkyl, hydroalkyl, carboalkyl, alkoxy, amino, alkenyl, aryl and CH2 Ar (where Ar is aryl or substituted aryl), preferably containing 1 to 6 carbons, more preferably 1 or 2 carbons, or a silane containing 1 to 6 silicon atoms; wherein, where an R1, R2, R3, R4, R18, R19, R20, R21, R22, R23, R24 and/or R25 group is not present an unsaturated bond is formed; preferably R1, R2, R3 and R4 are identical to R21, R20, R19 and R18 respectively; Preferably R5 and R17 are selected from H, xe2x80x94NH2, xe2x80x94OH substituted or non-substituted straight or branched chain alkyl or aryl, and halide, preferably the alkyl or aryl is a C1, to C6 alkyl or aryl, more preferably R5 and R17 being both the same. R5 and R17 may especially be H; R6, R7, R15 and R16 are each independently selected from halide xe2x80x94OH, xe2x80x94SO2R26, xe2x80x94SH, xe2x80x94NO2, xe2x80x94NH2, straight chain, branched chain, cyclic, saturated, non-saturated, substituted or non-substituted alkyl, carboalkyl, alkoxy, alkenyl, aryl and CH2 Ar (where Ar is aryl or substituted aryl), preferably containing 1 to 6 carbons, more preferably 1 or 2 carbons, or a silane containing 1 to 6 silicon atoms, wherein preferably R6 and R7 are identical to R15 and R16 respectively; R8 and R14 are selected from H, straight, branched, cyclic, saturated, non-saturated, substituted or non-substituted alkyl, carboalkyl, alkoxy, alkenyl, aryl and CH2 Ar (where Ar is aryl or substituted aryl), preferably containing 1 to 6 carbons, phenyl or substituted phenyl being especially preferred, R8 and R14 being preferably identical; R9, R10, R11, R12, R13 are independently selected from halide xe2x80x94OH, xe2x80x94SO2R26, xe2x80x94SH, xe2x80x94NO2, xe2x80x94NH2, straight chain, branched chain, cyclic, saturated, non-saturated, substituted or non-substituted alkyl, carboalkyl, alkoxy, amino, alkenyl, aryl and CH2 Ar (where Ar is aryl or substituted aryl), preferably containing 1 to 6 carbons, more preferably 1 or 2 carbons, or a silane, containing 1 to 6 silicon atoms, most preferably R9 is OMe, R10, R11, R12 and R13 preferably being each H; X is a linking group containing 1 to 12 atoms, preferably the linking group being selected from xe2x80x94Sxe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94Oxe2x80x94, straight chain, branched chain, cyclic, substituted or non-substituted alkyl, carboalkyl, alkoxy, alkenyl and aryl, preferably X containing 1 to 6 carbon atoms, most preferably X is a disubstituted aromatic moiety.
Preferably the invention provides compounds according to the first aspect of the invention with the provisos that together A is not CH2; R1, R2, R3, R4, R5, R6, R7, R10, R 11, R12 and R13 are not each H, R8 is not Ph; and R9 is not xe2x80x94OMe.
The compounds of the invention contain a chiral environment which is both rigid in structure and which, when complexed to a transition metal to form a catalyst, is located in close proximity to the metal reaction centre. Both of these features appear to account for the high asymmetric inductions observed by the inventors.
Having a xe2x80x94OMe group at position R9 has been found to improve the selectivity of the compounds when used as catalysts. Furthermore, an aromatic group at R8 in the case of compounds of Formula 1 and R8 and R14 in the case of Formula 2, has also been found to improve the selectivity of the compounds when used as catalysts.
Preferably the compound, according to Formula 1 the first aspect of the invention, has a formula according to Formula 3; 
With respect to Formula 2, the groups on each side of linking group X are preferably identical, to facilitate easier production of the ligand compound.
Preferably the compounds of Formula 2 of the invention have a general Formula 4: 
More preferably the compounds of this aspect of the invention have a formula according to Formula 5; 
In use the compounds of the invention are chelated with at least one metal ion to form a catalytic compound. Accordingly a second aspect of the invention provides a catalytic compound comprising a compound according to the first aspect of the invention chelated to at least one transition metal ion.
Preferably the transition metal ion is selected from palladium, ruthenium, rhodium, tungsten, nickel, platinum, copper, cobalt, zinc and molybdenum. The complexation methods used are those known in the art.
A third aspect of the invention provides a chemical formulation or composition, comprising either a compound according to the first aspect of the invention or a catalyst according to the second aspect of the invention.
A fourth aspect of the invention provides a process for carrying out a chemical reaction comprising reacting reactants in the presence of a catalyst according to the second aspect of the invention. Preferably the chemical reaction is an organic asymmetric catalysis reaction.
The compounds and catalysts of the invention allow high levels of enantiomeric excess (e.e.) and percentage yield to be produced. Enantiomeric excess is defined as (% major enantiomer)xe2x88x92(% minor enantiomer). A compound of high enantiomeric excess preferably exhibits an enantiomeric excess of  greater than 80%, especially  greater than 90%. A compound of very high e.e. exhibits an e.e. of  greater than 95%.
Preferably the asymmetric catalysis reaction is asymmetric hydrogenation. This technique is demonstrated in, for example, the papers by Burk et al (1993, 1998xe2x80x94Supra). A hydrogenation process comprising providing a substrate containing a reducible double bond dissolved in an inert solvent together with a catalyst according to the second aspect of the invention under a pressure of hydrogen of at least 1 atmosphere, stirring the reaction to completion, and isolating the product.
Preferably the metal in the catalyst is rhodium.
The asymmetric catalyst reaction may be allylic substitution. This is shown in, for example, Constantieux T. et al. (Synlett, (1998), page 49), Hayashi et al. (J. Am. Chem. Soc., (1994), Vol. 116, pages 775-776) and O""Donnell M. J. et al. (J. Org. Chem., (1997), Vol. 62, pages 3962-3975). Accordingly, the invention provides a process for allylic substitution comprising, providing solution of a substrate containing an appropriate allylic leaving group dissolved in an inert solvent, together with a catalyst according to the second aspect of the invention (preferably with palladium) and a co-reagent (preferably a malonate or an amine), and stirring for a period of time until reaction is deemed to be complete and then stopping the reaction prior to isolating the product.
Asymmetric hydroformylation, hydrovinylation and copolymerisation may also be carried out by methods known in the art. Accordingly the invention provides a process for asymmetric hydroformylation comprising providing a solution of a substrate containing an appropriate double bond dissolved in an inert solvent together with a catalyst according to the second aspect (preferably with rhodium) under an appropriate pressure of carbon monoxide and hydrogen, the solution being stirred for a period of time until reaction is deemed to be complete, and it is then stopped and the product isolated. Based on Nozaki el al., J. Org. Chem., 1997, 62, 4285.
A further aspect provides a process for asymmetric hydrovinylation comprising providing a solution of a substrate containing an appropriate double bond dissolved in an inert solvent together with a catalyst according to the second aspect of the invention (preferably with nickel) under an appropriate pressure of ethene, the solution being stirred for a period of time until reaction is deemed to be complete and is then stopped and the product isolated. Based on Rajanbabu et al. J. Am. Chem. Soc. 1998, 120, page 459.
A further aspect of the invention provides a process for asymmetric copolymerisation comprising providing a solution of a substrate containing an appropriate double bond dissolved in an inert solvent together with a catalyst according to the second aspect of the invention (preferably with palladium) under an appropriate pressure of carbon monoxide and propene, the solution being stirred for a period of time until reaction is deemed to be complete and it is then stopped and the product isolated. Based on Z. Zhang and A. Sen, J. Am. Chem. Soc., 1995, 117, 4455.
Conjugate addition reactions may also be carried out using the catalysts of the invention. Such reactions are described in, for example, Feringa et al. (Angew. Chem. Int. Ed. Engl., (1997), Vol. 36, page 2620). The invention therefore provides an asymetric conjugation addition process comprising providing a solution of a copper(II) salt together with a catalyst according to a second aspect of the invention stirring in an inert solvent under a nitrogen atmosphere, the substrate containing a suitable double bond and an appropriate source of alkyl group (preferably diethylzinc) is then added and the mixture stirred until the reaction is deemed to be complete at which point the product is isolated.
Alternatively, the catalysts of the invention may be used for asymmetric hydrosilylation. Such processes are described in Hayashi el al. Tet. Lett. (1996), Vol. 37, page 4169). The invention provides a process for asymmetric hydrosilylation comprising providing a solution of an appropriate substrate containing a reactive double bond, stirring with a complex of a catalyst according to the second aspect of the invention (preferably with palladium or rhodium) and a silyl-based reducing agent (preferably H3SiCl or Ph2SiH2) in an inert solvent under a nitrogen atmosphere until the reaction is deemed to be complete as which point the product is isolated.
The invention also includes products having high levels of e.e. obtainable by the processes according to the fourth aspect of the invention.
A fifth aspect of the invention provides a process for the production of a compound according to Formula 1, comprising the steps of:
a) providing a compound of Formula 6: 
where: R9-R13 are as previously defined.
b) mixing the compound of Formula 6 with a compound of Formula 7: 
where: R1-R8, and A, are as previously defined;
and
c) heating the mixture to form a compound of Formula 1.
Preferably the mixture in step c) is refluxed. The heating step c) may be carried out under nitrogen. The components in step b) may be mixed in an organic solvent such as toluene.
Preferably the compound of Formula 6 and the compound of Formula 7 are added in substantially equimolar concentrations.
A sixth aspect of the invention provides a process for the production of a compound according to Formula 2, comprising the steps of:
a) providing a compound having a formula X (P(NMe2)2)2 where X is as previously defined;
b) mixing with a compound of Formula 7 as defined above; and
c) heating.
Preferably the component in step a) has Formula 8: 
Preferably step c) is carried out by refluxing and may, preferably be carried out under nitrogen. An organic solvent, such as toluene may be used in step b).
Preferably approximately 2 moles of compound of Formula 7 are added to each mole of compound 8.
This process is relatively easy and cost efficient compared with some prior art processes.